The goal of this FIRCA is to identify genes responsible for schizophrenia in consanguineous Palestinian families. The rationale for the project is that schizophrenia may be caused by rare severe mutations in genes involved in neurodevelopment, and that individuals with schizophrenia in consanguineous, severely affected families may harbor such mutations as recessive alleles. The parent grant of the FIRCA is "A Genomic Approach to Schizophrenia" (1 R01 MH083989). The Palestinian PI of the FIRCA is Hashem Shahin, PhD, Assistant Professor of Biological Sciences at Bethlehem University. As the result of ten years collaboration with the King lab on genomic analysis of inherited hearing loss in Palestinian families, Dr Shahin is experienced with gene discovery using homozygosity mapping, CNV analysis, and, most recently, next generation sequencing. This FIRCA is Dr Shahin's first application for a research grant. The FIRCA project has three aims. Aim 1. With Dr Issam Bannoura, Director of the Bethlehem Mental Hospital, Dr. Shahin will ascertain and enroll families severely affected with schizophrenia. Aim 2. At Bethlehem University, Dr. Shahin will carry out homozygosity mapping and analysis of homozygous copy number variants, both using the Affymetrix platform. In the King lab at University of Washington, he will carry out next generation sequencing of linked regions identified by the homozygosity scans and captured using custom arrays. Aim 3. Again at Bethlehem University, Dr. Shahin will validate and characterize candidate mutations. At each step, new technology will be transferred to Bethlehem. FIRCA support will enable ~15 multiplex families to be evaluated. If this homozygosity mapping-based approach to gene discovery reveals new genes for schizophrenia, FIRCA results will be used to propose a project of wider scope. PUBLIC HEALTH RELEVANCE: The goal of this proposal for a Fogarty International Research Collaboration Award (FIRCA) is to identify genes responsible for schizophrenia in consanguineous Palestinian families. The rationale for the project is that schizophrenia may be caused by rare severe mutations in genes involved in neurodevelopment, and that individuals with schizophrenia in consanguineous, severely affected families may harbor such mutations as recessive alleles. If this project reveals new genes for schizophrenia, the results will be used to propose a project of wider scope.